Much remains to be known about the mechanisms involved in protective immunity against malaria and the way it is acquired. This is probably the reason why, in spite of so much progress, it has not yet been possible to develop an anti-malaria vaccine able to induce parasite specific antibodies (Ab) and/ or T-cells. It has been considered in the early 80s that the induction of efficient protection against the blood stage forms of Plasmodium falciparum would not be possible without simultaneously eliciting an autoimmune (AI) response against erythrocytes, even at the price of inducing an AI pathology. Despite the description of the reciprocal relationship, i.e. the protective effect of malaria on the development of AI diseases – demonstrated since 1970 – no effort has been made to verify the possible involvement of the AI response in protection against malaria. With this end in view – and in the light of the knowledge acquired in autoimmunity and the existence of the so called “natural” (not associated with pathology) autoantibodies – we propose to examine the hypothesis that the participation of the AI response (not necessarily restricted to autologous erythrocyte antigens) in the immune protection against malaria is possible or even necessary.